Understanding the yeast host cell response to recombinant membrane protein production

Membrane proteins are drug targets for a wide range of diseases. Having access to appropriate samples for further research underpins the pharmaceutical industry's strategy for developing new drugs. This is typically achieved by synthesizing a protein of interest in host cells that can be cultured on a large scale, allowing the isolation of the pure protein in quantities much higher than those found in the protein's native source. Yeast is a popular host as it is a eukaryote with similar synthetic machinery to that of the native human source cells of many proteins of interest, while also being quick, easy and cheap to grow and process. Even in these cells, the production of human membrane proteins can be plagued by low functional yields; we wish to understand why. We have identified molecular mechanisms and culture parameters underpinning high yields and have consolidated our findings to engineer improved yeast host strains. By relieving the bottlenecks to recombinant membrane protein production in yeast, we aim to contribute to the drug discovery pipeline, while providing insight into translational processes.

Authors' response:clinical evaluation of the MPS 9000 macular pigment screener

As a research group with no commercial interest in any macular pigment optical density (MPOD) measurement devices or nutritional supplements, we feel that we were well-placed to carry out an independent clinical assessment of the reliability of the MPS 9000 (Tinsley Precision Instruments, Redhill, Surrey, UK). Our study was prompted by the fact that we could not find any reported coefficient of repeatability value within the literature, and none was provided by the manufacturer.1 We had planned to use this instrument in our own research studies investigating the impact of nutritional supplementation on MPOD. For this purpose, we needed …

The state of the art in organizational cognitive neuroscience:the therapeutic gap and possible implications for clinical practice

In the last decade, researchers in the social sciences have increasingly adopted neuroscientific techniques, with the consequent rise of research inspired by neuroscience in disciplines such as economics, marketing, decision sciences, and leadership. In 2007, we introduced the term organizational cognitive neuroscience (OCN), in an attempt to clearly demarcate research carried out in these many areas, and provide an overarching paradigm for research utilizing cognitive neuroscientific methods, theories, and concepts, within the organizational and business research fields. Here we will revisit and further refine the OCN paradigm, and define an approach where we feel the marriage of organizational theory and neuroscience will return even greater dividends in the future and that is within the field of clinical practice.

Sensing applications of arrayed waveguide grating devices

Progress in optical fibre sensor research has often been achieved by taking advantage of components developed for use in telecommunications, where the greater existing market is able to support the rapid commercialisation of novel devices. In the last few years there has been considerable interest in the telecommunications community in deploying arrayed waveguide gratings (AWGs) produced in a range of technologies in a variety of roles. We feel it is therefore surprising that there have been very few reports of research into using AWGs for sensing. In this paper we consider some possible roles for these devices in interrogation systems for interferometric and fibre Bragg grating (FBG) sensors.

Editorial

The year so far has been a slow start for many businesses, but at least we have not seen the collapse of as many businesses that we were seeing around two years ago. We are, however, still well and truly in the midst of a global recession. Interest rates are still at an all time low, UK house prices seem to be showing little signs of increase (except in London where everyone still seems to want to live!) and for the ardent shopper there are bargains to be had everywhere. It seems strange that prices on the high street do not seem to have increased in over ten years. Mobile phones, DVD players even furniture seems to be cheaper than they used to be. Whist much of this is down to cheaper manufacturing and the rest could probably be explained by competition within the market place. Does this mean that quality suffered too? Now that we live in a world when if a television is not working it is thrown away and replaced. There was a time when you would take it to some odd looking man that your father would know who could fix it for you. (I remember our local television fix-it man, with his thick rimmed bifocal spectacles and a poor comb-over; he had cardboard boxes full of resistors and electrical wires on the floor of his front room that smelt of soldering irons!) Is this consumerism at an extreme or has this move to disposability made us a better society? Before you think these are just ramblings there is a point to this. According to latest global figures of contact lens sales the vast majority of contact lenses fitted around the world are daily, fortnightly or monthly disposable hydrogel lenses. Certainly in the UK over 90% of lenses are disposable (with daily disposables being the most popular, having a market share of over 50%). This begs the question – is this a good thing? Maybe more importantly, do our patients benefit? I think it is worth reminding ourselves why we went down the disposability route with contact lenses in the first place, and unlike electrical goods it was not just so we did not have to take them for repair! There are the obvious advantages of overcoming problems of breakage and tearing of lenses and the lens deterioration with age. The lenses are less likely to be contaminated and the disinfection is either easier or not required at all (in the case of daily disposable lenses). Probably the landmark paper in the field was the work more commonly known as the ‘Gothenburg Study’. The paper, entitled ‘Strategies for minimizing the Ocular Effects of Extended Contact Lens Wear’ published in the American Journal of Optometry in 1987 (volume 64, pages 781-789) by Holden, B.A., Swarbrick, H.A., Sweeney, D.F., Ho, A., Efron, N., Vannas, A., Nilsson, K.T. They suggested that contact lens induced ocular effects were minimised by: •More frequently removed contact lenses •More regularly replaced contact lenses •A lens that was more mobile on the eye (to allow better removal of debris) •Better flow of oxygen through the lens All of these issues seem to be solved with disposability, except the oxygen issue which has been solved with the advent of silicone hydrogel materials. Newer issues have arisen and most can be solved in practice by the eye care practitioner. The emphasis now seems to be on making lenses more comfortable. The problems of contact lens related dry eyes symptoms seem to be ever present and maybe this would explain why in the UK we have a pretty constant contact lens wearing population of just over three million but every year we have over a million dropouts! That means we must be attracting a million new wearers every year (well done to the marketing departments!) but we are also losing a million wearers every year. We certainly are not losing them all to the refractive surgery clinics. We know that almost anyone can now wear a contact lens and we know that some lenses will solve problems of sharper vision, some will aid comfort, and some will be useful for patients with dry eyes. So if we still have so many dropouts then we must be doing something wrong! I think the take home message has to be ‘must try harder’! I must end with an apology for two errors in my editorial of issue 1 earlier this year. Firstly there was a typo in the first sentence; I meant to state that it was 40 years not 30 years since the first commercial soft lens was available in the UK. The second error was one that I was unaware of until colleagues Geoff Wilson (Birmingham, UK) and Tim Bowden (London, UK) wrote to me to explain that soft lenses were actually available in the UK before 1971 (please see their ‘Letters to the Editor’ in this issue). I am grateful to both of them for correcting the mistake.

Reply to "comment on 'Optical rogue waves in telecommunication data streams'"

We feel that the main claim made in the abstract of the preceding Comment is wrong. Using results obtained in our paper, we prove that rogue waves with amplitudes much larger than the average level can be observed during a short period of time in purely linear propagation regimes in optical fiber systems. © 2011 American Physical Society.

Why is Werner Sombart not part of the core of classical sociologists? From fame to (near) oblivion:From Fame to (Near) Oblivion

The life and work of Werner Sombart poses an intellectual puzzle in the genealogy of modern social theorists. During his lifetime, Sombart was probably the most influential and prominent social scientist in Germany as well as in many other countries. Today he is among the least known social scientists. Why did he lose his status as one of the most brilliant and influential scholars and intellectuals of the 20th century? Why is his work almost forgotten today? While Weber's thesis about the influence of Protestantism on the development of capitalism is widely known, even beyond sociological circles, few sociologists today know that Sombart had an alternative explanation. An obvious explanation for Sombart's fall from grace is his embrace of Nazism. As Heidegger provides a counter-example, Sombart's fate requires a more complex explanation. In addition, we explore the different reception of his work in economic and sociological circles as compared to cultural theory and history. © 2001, SAGE Publications. All rights reserved.

Why are health care interventions delivered over the internet? A systematic review of the published literature

Background: As Internet use grows, health interventions are increasingly being delivered online. Pioneering researchers are using the networking potential of the Internet, and several of them have evaluated these interventions. Objective: The objective was to review the reasons why health interventions have been delivered on the Internet and to reflect on the work of the pioneers in this field in order to inform future research. Methods: We conducted a qualitative systematic review of peer-reviewed evaluations of health interventions delivered to a known client/patient group using networked features of the Internet. Papers were reviewed for the reasons given for using the Internet, and these reasons were categorized. Results: We included studies evaluating 28 interventions plus 9 interventions that were evaluated in pilot studies. The interventions were aimed at a range of health conditions. Reasons for Internet delivery included low cost and resource implications due to the nature of the technology; reducing cost and increasing convenience for users; reduction of health service costs; overcoming isolation of users; the need for timely information; stigma reduction; and increased user and supplier control of the intervention. A small number of studies gave the existence of Internet interventions as the only reason for undertaking an evaluation of this mode of delivery. Conclusions: One must remain alert for the unintended effects of Internet delivery of health interventions due to the potential for reinforcing the problems that the intervention was designed to help. Internet delivery overcomes isolation of time, mobility, and geography, but it may not be a substitute for face-to-face contact. Future evaluations need to incorporate the evaluation of cost, not only to the health service but also to users and their social networks. When researchers report the outcomes of Internet-delivered health care interventions, it is important that they clearly state why they chose to use the Internet, preferably backing up their decision with theoretical models and exploratory work. Evaluation of the effectiveness of a health care intervention delivered by the Internet needs to include comparison with more traditional modes of delivery to answer the following question: What are the added benefits or disadvantages of Internet use that are particular to this mode of delivery? © Griffiths, Frances, Lindenmeyer, Antje, Powell, John, Thorogood, Margaret.

Why critical pedagogy and popular education matter today

Few today doubt that English Higher Education (HE), like the wider world in which it is located, is in crisis. This is, in part, an economic crisis, as the government response to the current recession seems to be that of introducing the kind of neoliberal ‘shock doctrine’ (Klein 2007) or ‘shock therapy’ (Harvey 2005) that previously resulted in swingeing cuts in public services in Southern nations. Our aim in producing this volume is that these contributions help develop a collective response to the seeming limits of these conditions. We view the strength of these contributions in part as providing palpable evidence of how we and our colleagues are acting with critical hope under current conditions so that we might encourage others to work with us to build, together, more progressive formal and informal education systems that address and seek to redress multiple injustices of the world today.

Why are MD simulated protein folding times wrong?

The question of significant deviations of protein folding times simulated using molecular dynamics from experimental values is investigated. It is shown that in the framework of Markov State Model (MSM) describing the conformational dynamics of peptides and proteins, the folding time is very sensitive to the simulation model parameters, such as forcefield and temperature. Using two peptides as examples, we show that the deviations in the folding times can reach an order of magnitude for modest variations of the molecular model. We, therefore, conclude that the folding rate values obtained in molecular dynamics simulations have to be treated with care.

Why are optimistic entrepreneurs successful? An application of the regulatory focus theory

Does entrepreneurial optimism affect business performance? Using a unique data set based on repeated survey design, we investigate this relationship empirically. Our measures of ëoptimismí and ërealismí are derived from comparing the turnover growth expectations of ...133 owners-managers with the actual outcomes one year later. Our results indicate that entrepreneurial optimists perform significantly better in terms of profits than pessimists. Moreover, it is the optimist-realist combination that performs best. We interpret our results using regulatory focus theory.

Why are optimistic entrepreneurs successful? An application of the regulatory focus theory

Does entrepreneurial optimism affect business performance? Using a unique data set based on repeated survey design, we investigate this relationship empirically. Our measures of ‘optimism’ and ‘realism’ are derived from comparing the turnover growth expectations of 133 owners-managers with the actual outcomes one year later. Our results indicate that entrepreneurial optimists perform significantly better in terms of profits than pessimists. Moreover, it is the optimist-realist combination that performs best. We interpret our results using regulatory focus theory.

Ties that bind:understanding why and how diversity management relates to black and ethnic minority employees’ experience of organisational life

Despite much anecdotal and oftentimes empirical evidence that black and ethnic minority employees do not feel integrated into organisational life and the implications of this lack of integration for their career progression, there is a dearth of research on the nature of the relationship black and ethnic minority employees have with their employing organisations. Additionally, research examining the relationship between diversity management and work outcomes has returned mixed findings. Scholars have attributed this to the lack of an empirically validated measure of workforce diversity management. Accordingly, I sought to address these gaps in the extant literature in a two-part study grounded in social exchange theory. In Study 1, I developed and validated a measure of workforce diversity management practices. Data obtained from a sample of ethnic minority employees from a cross section of organisations provided support for the validity of the scale. In Study 2, I proposed and tested a social-exchange-based model of the relationship between black and ethnic minority employees’ and their employing organisations, as well as assessed the implications of this relationship for their work outcomes. Specifically, I hypothesised: (i) perception of support for diversity, perception of overall justice, and developmental experiences (indicators of integration into organisational life) as mediators of the relationship between diversity management and social exchange with organisation; (ii) the moderating influence of diversity climate on the relationship between diversity management and these indicators of integration; and (iii) the work outcomes of social exchange with organisation defined in terms of career satisfaction, turnover intention and strain. SEM results provide support for most of the hypothesised relationships. The findings of the study contribute to the literature on workforce diversity management in a number of ways. First, the development and validation of a diversity management practice scale constitutes a first step in resolving the difficulty in operationalising and measuring the diversity management construct. Second, it explicates how and why diversity management practices influence a social exchange relationship with an employing organisation, and the implications of this relationship for the work outcomes of black and ethnic minority employees. My study’s focus on employee work outcomes is an important corrective to the predominant focus on organisational-level outcomes of diversity management. Lastly, by focusing on ethno-racial diversity my research complements the extant research on such workforce diversity indicators as age and gender.

Why is it possible to detect doped regions of semiconductors in low voltage SEM:a review and update

There is an urgent need for fast, non-destructive and quantitative two-dimensional dopant profiling of modern and future ultra large-scale semiconductor devices. The low voltage scanning electron microscope (LVSEM) has emerged to satisfy this need, in part, whereby it is possible to detect different secondary electron yield values (brightness in the SEM signal) from the p-type to the n-type doped regions as well as different brightness levels from the same dopant type. The mechanism that gives rise to such a secondary electron (SE) contrast effect is not fully understood, however. A review of the different models that have been proposed to explain this SE contrast is given. We report on new experiments that support the proposal that this contrast is due to the establishment of metal-to-semiconductor surface contacts. Further experiments showing the effect of instrument parameters including the electron dose, the scan speeds and the electron beam energy on the SE contrast are also reported. Preliminary results on the dependence of the SE contrast on the existence of a surface structure featuring metal-oxide semiconductor (MOS) are also reported. Copyright © 2005 John Wiley & Sons, Ltd.

Why are aggregate equity payouts pro-cyclical?

We use two general equilibrium models to explain why changes in the external economic environment result in pro-cyclical aggregate dividend payout behavior. Both models that we consider endogenize low elasticity of investment. The first model incorporates capital adjustment costs, while the second one assumes that risk-averse managers maximize their own objective function rather than shareholder wealth. We show that, while both models generate pro-cyclical aggregate dividends, a feature consistent with the observed business-cycle pattern of payouts from well-diversified portfolios, the second model provides a more likely explanation for this effect. Our findings emphasize the importance of incorporating agency conflicts when considering the relationship between the external economic environment and the financial behavior of businesses.